Evidence map›Paper›PMID 42552599›Full record

ArticleCNS neuroscience & therapeutics2026

N6-Methyladenosine Demethylase FTO Mitigates Cerebral Ischemia-Reperfusion Injury by Suppressing AQP4 Expression.

Wei Chen, Luyuan Cao, Xiaoxiao Zheng, Chenyuan Yu, Xiaoqiang Zhu, Qing Wang, Li Zheng, Jiahua Lan, Cheng Jiang, Hongwei Wang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in CNS neuroscience & therapeutics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Wei ChenProvincial Key Laboratory of Precise Diagnosis and Treatment of Abdominal Infection, Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.ORCID https://orcid.org/0000-0002-0399-6216
Luyuan CaoSchool of Basic Medical Sciences and Forensic Medicine, Hangzhou Medical College, Hangzhou, Zhejiang, China.
Xiaoxiao ZhengCancer Institute of Integrated Traditional Chinese and Western Medicine, Key Laboratory of Cancer Prevention and Therapy Combining Traditional Chinese and Western Medicine of Zhejiang Province, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, China.
Chenyuan YuDepartment of Anesthesiology, Tongde Hospital of Zhejiang Province, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, Zhejiang, China.
Xiaoqiang ZhuDepartment of Anesthesiology, Tongde Hospital of Zhejiang Province, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, Zhejiang, China.
Qing WangDepartment of Anesthesiology, Tongde Hospital of Zhejiang Province, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, Zhejiang, China.
Li ZhengCancer Institute of Integrated Traditional Chinese and Western Medicine, Key Laboratory of Cancer Prevention and Therapy Combining Traditional Chinese and Western Medicine of Zhejiang Province, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, China.
Jiahua LanCancer Institute of Integrated Traditional Chinese and Western Medicine, Key Laboratory of Cancer Prevention and Therapy Combining Traditional Chinese and Western Medicine of Zhejiang Province, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, China.
Cheng JiangCancer Institute of Integrated Traditional Chinese and Western Medicine, Key Laboratory of Cancer Prevention and Therapy Combining Traditional Chinese and Western Medicine of Zhejiang Province, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, China.ORCID https://orcid.org/0000-0001-8454-749X
Hongwei WangSchool of Basic Medical Sciences and Forensic Medicine, Hangzhou Medical College, Hangzhou, Zhejiang, China.

Funding

Medical Science and Technology Project of Zhejiang Province 2025ZR085National Natural Science Foundation of China 82174132National Natural Science Foundation of China 82374293National Natural Science Foundation of China-Guangdong Joint Fund 2020A151501287the General Project of Science and Technology Innovation Commission of Shenzhen JCYJ20190808103401655
6 · The paper itself

Abstract

aimIn patients with acute ischemic stroke, reperfusion therapy can compromise the blood-brain barrier, resulting in secondary cerebral ischemia-reperfusion injury (CIRI). This study investigated the involvement of the N6-methyladenosine (m6A) demethylase FTO in the pathogenesis of CIRI and explored the underlying molecular mechanisms.

methodsWe established a middle cerebral artery occlusion (MCAO) mouse model in vivo and an oxygen-glucose deprivation/reperfusion (OGD/R) model in primary astrocytes in vitro.

resultsFTO expression was significantly downregulated in both the in vivo and in vitro CIRI models. Upregulation of FTO via plasmid transfection significantly attenuated cellular damage and enhanced astrocyte viability. At the molecular level, m6A-modified transcripts were enriched in the MAPK signaling pathway during cerebral ischemia-reperfusion. Notably, Heat Shock Protein Family A (Hsp70) Member 1A (Hspa1a) was identified as a key target. The reduction in FTO expression led to increased m6A methylation levels on Hspa1a mRNA, thereby promoting its degradation. Furthermore, the cellular damage induced by FTO silencing was alleviated by Hspa1a overexpression or the silencing of Aquaporin-4 (AQP4).

conclusionsThis study demonstrates that FTO mitigates CIRI by stabilizing Hspa1a mRNA, which in turn suppresses AQP4 expression. Consequently, FTO represents a promising therapeutic target for the treatment of ischemic stroke.

Indexed as

Alpha-Ketoglutarate-Dependent Dioxygenase FTOAquaporin 4Brain IschemiaReperfusion InjuryAdenosineAnimalsAstrocytesCells, CulturedInfarction, Middle Cerebral ArteryMaleMiceMice, Inbred C57BLAdenosineAlpha-Ketoglutarate-Dependent Dioxygenase FTOAqp4 protein, mouseAquaporin 4FTO protein, mouseN-methyladenosineAQP4cerebral ischemia–reperfusion injuryFTOHspa1am6A modification

Identifiers

PMID42552599
PMCPMC13437947

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.